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Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder

Paul Saenger1* and Edward Reiter2

Author Affiliations

1 Albert Einstein College of Medicine, Winthrop University Hospital, 120 Mineola Boulevard, Mineola, NY, 13501, USA

2 Baystate Children’s Hospital, Tufts University School of Medicine, 759 Chestnut Street, Springfield, MA, 01199, USA

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International Journal of Pediatric Endocrinology 2012, 2012:12  doi:10.1186/1687-9856-2012-12

Published: 15 May 2012


The term small for gestational age (SGA) refers to infants whose birth weights and/or lengths are at least two standard deviation (SD) units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS) deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR) polymorphism. Uniparental disomy (UPD) and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH) therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

Growth hormone; Small for gestational age; Insulin-like growth factor; Acid-labile subunit deficiency; Uniparental disomy